Diaphragmatic function is enhanced in fatty and diabetic fatty rats

PLoS One. 2017 Mar 22;12(3):e0174043. doi: 10.1371/journal.pone.0174043. eCollection 2017.

Abstract

Background: Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function.

Methods: Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways.

Results: Diaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P<0.001, respectively) and a smaller CSA of MyHC-2X in fatty compared with diabetic fatty and control rats (P<0.001 and P<0.001, respectively). The phosphorylated total-protein-kinase-B (pAKT)/AKT ratio was higher in fatty (182±58%,P = 0.03), but not in diabetic fatty when compared with controls and monocarboxylate-transporter-1 was higher in diabetic fatty (147±36%,P = 0.04), but not in fatty.

Conclusions: Diaphragmatic force is increased in Zucker obese rats before and after mechanical ventilation, and is associated with activation of AKT pathway signaling and complex changes in morphology.

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology*
  • Diaphragm / metabolism*
  • Diaphragm / physiology*
  • Male
  • Monocarboxylic Acid Transporters / metabolism
  • Muscle Contraction / physiology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Prospective Studies
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Zucker
  • Signal Transduction / physiology

Substances

  • Monocarboxylic Acid Transporters
  • Proto-Oncogene Proteins c-akt

Grant support

Support was provided solely from institutional and/or departmental sources. Dr. Cheng Jiang was the recipient of a doctoral grant from the People’s Republic of China (the State Scholarship Fund by China Scholarship Council, file n° 201206270014). The sponsor had no role in the analysis or reporting of the data.